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Toxicity assessment of (99m)technetium-labeled human beta-defensin-3 in CD1 mice
Mauro Liberatore1, Christos Anagnostou, Sergio Scaccianoce
1Department of Radiological, Oncological and Anatomo-Pathological Sciences, "Sapienza" University of Roma, Italy. chr.anagnostou@yahoo.it.
Objective:
Human beta-defensin-3 (HBD-3) is an antimicrobial peptide which is up-regulated during inflammation. Based on the previously demonstrated capacity of technetium-99m ((99m)Tc) labelled HBD-3 of distinguishing infection from inflammation in rats, we have decided to collect information on the potential toxicity of the tracer in view of its possible use for imaging in humans.
Materials And Methods:
Recombinant HBD-3 underwent labeling with (99m)Tc. The CD1 mice were selected as standard rodent species. Ten mice, 5 male and 5 female, were subjected to physical examination and housed in a dedicated room in 5 per cage. After 9 days pre-test period, all mice were weighted for dose adjustment and received intravenously 6mcg/mouse of (99m)Tc-HBD-3. Mortality was recorded daily, while body weight was registered once a week. Clinical observation of animals was performed daily for sickness symptoms due to the drug treatment. At day 19 a second dose of 6mcg/mouse (99m)Tc-HBD-3, was administered. Twenty-four hours after the second dose (day 20) the animals were euthanized. A piece of liver, kidneys, heart and lungs was collected for histopathological analysis.
Results:
Our results showed that the labelled-HBD-3 dose did not induce significant toxicity in mice. Of course these parameters were not sufficient to authorize use in humans. This non-toxic dose of HBD-3 when translated from animals to humans resulted in an equivalent dose of approximately 25 times higher than that needed for imaging.
Conclusion:
Our non toxicity data of using (99m)Tc-beta-defensin-3 in mice offer a further indication in favour of the clinical use of this radiopharmaceutical in all cases where discrimination between infection and inflammation is needed.
Insights
Technetium-99m labelled human beta-defensin-3 ((99m)Tc-HBD-3) showed no significant toxicity in mice. These findings support the potential clinical use of (99m)Tc-HBD-3 for distinguishing infection from inflammation.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical development
- Antimicrobial peptides
Background:
- Human beta-defensin-3 (HBD-3) is an antimicrobial peptide upregulated during inflammation.
- (99m)Tc-labeled HBD-3 has shown potential in distinguishing infection from inflammation in preclinical models.
Purpose of the Study:
- To evaluate the potential toxicity of (99m)Tc-labeled HBD-3 in mice.
- To gather data for potential human imaging applications.
Main Methods:
- Recombinant HBD-3 was labeled with (99m)Tc.
- CD1 mice received two intravenous doses of (99m)Tc-HBD-3.
- Mortality, body weight, and clinical signs were monitored.
- Histopathological analysis of major organs was performed.
Main Results:
- The (99m)Tc-HBD-3 dose did not induce significant toxicity in mice.
- The non-toxic dose in mice, when extrapolated to humans, is approximately 25 times higher than the imaging dose.
Conclusions:
- Non-toxicity data in mice support the potential clinical use of (99m)Tc-HBD-3.
- This radiopharmaceutical could aid in differentiating infection from inflammation.
